22. Kernicterus - Shapiro - Children's Mercy Kansas · PDF file10/29/12 2 P.I.C.K. Parents of...

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Steven Steven M. Shapiro M. Shapiro M.DM.D..November 16November 16, 2012, 2012

Clinical Advances in Pediatrics • Children’s Mercy Hospital & Clinics Clinical Advances in Pediatrics • Children’s Mercy Hospital & Clinics •• Kansas City, MOKansas City, MODivision of Neurology • Department of PediatricsDivision of Neurology • Department of Pediatrics

[email protected]@cmh.edu

Steven Steven M. Shapiro M. Shapiro M.DM.D..November 16November 16, 2012, 2012

Clinical Advances in Pediatrics • Children’s Mercy Hospital & Clinics Clinical Advances in Pediatrics • Children’s Mercy Hospital & Clinics •• Kansas City, MOKansas City, MODivision of Neurology • Department of PediatricsDivision of Neurology • Department of Pediatrics

[email protected]@cmh.edu

OutlineOutlineObjectives: •To understand the classical and subtle manifestations of neonatal bilirubin neurotoxicity

new definitions of kernicterus and bilirubin induced neurological disorders (BIND), •To understand that bilirubin neurotoxicity can cause auditory neuropathy spectrum

disorders (ANSD), which can be an unrecognized cause of speech and language delays.

1. Why care about bilirubin?2. How does bilirubin damage the brain?

Review of bilirubin metabolism

Objectives: •To understand the classical and subtle manifestations of neonatal bilirubin neurotoxicity

new definitions of kernicterus and bilirubin induced neurological disorders (BIND), •To understand that bilirubin neurotoxicity can cause auditory neuropathy spectrum

disorders (ANSD), which can be an unrecognized cause of speech and language delays.

1. Why care about bilirubin?2. How does bilirubin damage the brain?

Review of bilirubin metabolism

Children’s MercyHOSPITALS & CLINICS

Kansas City

– Review of bilirubin metabolism– Correlation of damage with total unconjugated and free bilirubin

3. What are the types of damage and clinical symptoms that result?– Classical definitions of kernicterus;– New definitions: motor and auditory subtypes (ANSD), BIND

4. Relationship of kernicterus subtypes to neurodevelopment at time of peak bilirubin level (prematures -> auditory/ANSD)

5. Mistakes that can lead to kernicterus6. How to know if bilirubin causes a neurological problem?7. Conclusion

– Review of bilirubin metabolism– Correlation of damage with total unconjugated and free bilirubin

3. What are the types of damage and clinical symptoms that result?– Classical definitions of kernicterus;– New definitions: motor and auditory subtypes (ANSD), BIND

4. Relationship of kernicterus subtypes to neurodevelopment at time of peak bilirubin level (prematures -> auditory/ANSD)

5. Mistakes that can lead to kernicterus6. How to know if bilirubin causes a neurological problem?7. Conclusion

Why care about newborn jaundice? Why care about newborn jaundice?

ll Visible jaundice occurs in 60% Visible jaundice occurs in 60% of of term and term and ~80% ~80% preterm infantspreterm infants

ll Bilirubin is bound to albumin in blood. When Bilirubin is bound to albumin in blood. When bilirubin levels bilirubin levels exceedexceed binding binding capacity of blood capacity of blood albumin, bilirubin moves into brain and causes albumin, bilirubin moves into brain and causes

ll Visible jaundice occurs in 60% Visible jaundice occurs in 60% of of term and term and ~80% ~80% preterm infantspreterm infants

ll Bilirubin is bound to albumin in blood. When Bilirubin is bound to albumin in blood. When bilirubin levels bilirubin levels exceedexceed binding binding capacity of blood capacity of blood albumin, bilirubin moves into brain and causes albumin, bilirubin moves into brain and causes


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,,brain damage called brain damage called kernicteruskernicterus..

“Kern“Kern--” ” deep nuclei or deep nuclei or kernelkernel of the brainof the brain““--icterus” icterus” from Greek = from Greek = yellowyellowKernicterusKernicterus = yellow staining of deep nuclei or = yellow staining of deep nuclei or kernelkernel of of

brainbrain

ll Prior to screening, treating and preventing Prior to screening, treating and preventing excessively high bilirubin levels, excessively high bilirubin levels, kernicterus kernicterus accounted accounted for for ~10~10% of % of cerebral palsy (CP)cerebral palsy (CP)

,,brain damage called brain damage called kernicteruskernicterus..

“Kern“Kern--” ” deep nuclei or deep nuclei or kernelkernel of the brainof the brain““--icterus” icterus” from Greek = from Greek = yellowyellowKernicterusKernicterus = yellow staining of deep nuclei or = yellow staining of deep nuclei or kernelkernel of of

brainbrain

ll Prior to screening, treating and preventing Prior to screening, treating and preventing excessively high bilirubin levels, excessively high bilirubin levels, kernicterus kernicterus accounted accounted for for ~10~10% of % of cerebral palsy (CP)cerebral palsy (CP)

Why care ? Why care ? l Excessive jaundice in newborns may cause

preventable brain damage, kernicterus, in neonate.l Kernicterus, can be extremely disabling and difficult to

treat, causing severe dystonia (abnormal muscle tone) and deafness or auditory neuropathy spectrum disorders (ANSD) yet normal cognitive function!

l Excessive jaundice in newborns may cause preventable brain damage, kernicterus, in neonate.l Kernicterus, can be extremely disabling and difficult to

treat, causing severe dystonia (abnormal muscle tone) and deafness or auditory neuropathy spectrum disorders (ANSD) yet normal cognitive function!


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yet normal cognitive function!l Children can be virtually “locked in.”

l Neonatal jaundice is very common problem with concern about a very rare but tragic sequelae –kernicterus!

l 1:100,000 live births (Denmark, Great Britain, ?USA)l ~25x higher without screening and treatment

yet normal cognitive function!l Children can be virtually “locked in.”

l Neonatal jaundice is very common problem with concern about a very rare but tragic sequelae –kernicterus!

l 1:100,000 live births (Denmark, Great Britain, ?USA)l ~25x higher without screening and treatment

Why care? Why care? l Re-emergence of kernicterus in the USA in

the 1990’s in part due to:l Due to early hospital discharge; lack of concern

l Brain damage (kernicterus) is preventable

l Re-emergence of kernicterus in the USA in the 1990’s in part due to:

l Due to early hospital discharge; lack of concern

l Brain damage (kernicterus) is preventable


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g pl Effects of bilirubin may be more prevalent

and different in prematurely born infantsl Excessive hyperbilirubinemia causes central

auditory processing e.g., auditory neuropathy spectrum disorders (ANSD) and may cause or contribute to learning disorders.

g pl Effects of bilirubin may be more prevalent

and different in prematurely born infantsl Excessive hyperbilirubinemia causes central

auditory processing e.g., auditory neuropathy spectrum disorders (ANSD) and may cause or contribute to learning disorders.

Front page of USA Today, October 2000


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P.I.C.K.Parents of Infants and Children with Kernicterus

P.I.C.K.Parents of Infants and Children with Kernicterus

Kernicterus, permanent brain damage due to

excessive newborn jaundice, is preventable with bilirubin

measurements and treatment.

www pickonline orgwww.pickonline.org

Jess, Age 11,Birmingham, Al.

.Krista, Age 9, Lexington, Ma.

Justin, Age 2, St. Paul, Mn.

Nathaniel, Age 3, Eagan, Mn.

David, Age 6, Eden Prairie, Mn.

Cal, Age 4, Boise, Id

www.kernicterus.org

Why care? JCAHO 2001Why care? JCAHO 2001

Issue 18, April 2001

Published for Joint Commission accredited organizations and interested health care professionals, Sentinel Event Alert identifies the most frequently occurring sentinel events, describes their

common underlying causes, and suggests steps to prevent occurrences in the future.


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y g , gg p p f

Kernicterus threatens healthy newborns

Kernicterus is a condition of newborns that leads to severely disabling brain damage or death. It results from hyperbilirubinemia that can be caused by a number of factors. Kernicterus is preventable with techniques currently available. Nevertheless, in recent years cases of kernicterus have continued to be reported. One registry includes 90 cases in the United States from 1984 to the present in which three of the newborns died and all others sustained brain damage.1 "This is probably happening more than clinicians know about," says Sue Sheridan, spokesperson for the advocacy, educational and support group PICK, Parents of Infants and Children with Kernicterus. "With these recent cases, risk assessments were inadequate and unreliable, and bilirubin levels were not measured--or measured in time." PICK has been instrumental in drawing attention to the reemergence of kernicterus and its prevention.


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Current concernsCurrent concerns•Kernicterus still occurs (1:100,000 LBs)

•Kernicterus may be the “tip of the iceberg.”

•Subtle kernicterus (aka BIND or bilirubin induced neurological disorders) may account for many more cases of:

•Kernicterus still occurs (1:100,000 LBs)

•Kernicterus may be the “tip of the iceberg.”

•Subtle kernicterus (aka BIND or bilirubin induced neurological disorders) may account for many more cases of:


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y– Learning disabilities,

– Central auditory processing disorders (ANSD),

– Dyslexia, oculomotor dyspraxia,

– Movement disorders, and

– Autism

– Adult disorders? May even predispose to Parkinson’s disease or schizophrenia

y– Learning disabilities,

– Central auditory processing disorders (ANSD),

– Dyslexia, oculomotor dyspraxia,

– Movement disorders, and

– Autism

– Adult disorders? May even predispose to Parkinson’s disease or schizophrenia

Newborn Jaundice and Autism – Oct 2010Newborn Jaundice and Autism – Oct 2010


Kansas City


Kansas City

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BloodBlood LiverLiver GutGutBrainBrain

UGST UGST

Conj.Bili

Bf

Biliverdin

heme heme oxygenaseoxygenase

CO

HemoglobinA.Conj.Bili

E. F.

B.biliverdinbiliverdin

reductasereductase

Bilirubin MetabolismBilirubin Metabolism

D. UCB

UCB

StooStooll

StooStooll

f

Bf

C. UCB

Albumin

Bf Bf UCB

AlbuminX

Shapiro, Pediatric Neurology 29:410, 2003Shapiro, Pediatric Neurology 29:410, 2003

--glucuronidaseglucuronidase--glucuronidaseglucuronidase

Why Bilirbuin? The neuroprotective effect of mild hyperbilirubinemia

Why Bilirbuin? The neuroprotective effect of mild hyperbilirubinemia


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l Q: Why do we make bilirubin?

l A: It is an antioxidant. A mechan-ism exists - the bilirubin-biliverdincycle to amplify the antioxidant effect of bilirubin 10,000 times.

l It “cleans up” reactive oxygen species produced by mild birth asphyxia.

l Q: Why do we make bilirubin?

l A: It is an antioxidant. A mechan-ism exists - the bilirubin-biliverdincycle to amplify the antioxidant effect of bilirubin 10,000 times.

l It “cleans up” reactive oxygen species produced by mild birth asphyxia.

Amplification of the neuroprotective effect of bilirubinby redox cycling. Biliverdin is reduced to bilirubin bybiliverdin reductase (BVR) and is regenerated whenthe detoxification of reactive oxygen species (ROS)oxidizes bilirubin back to biliverdin. In this manner,low concentrations of bilirubin can be recycled toneutralize large amounts of ROS. (Greenberg DA,PNAS 99:15837, 2002)

PNASPNAS 99:16093, 2002; PNAS 99:15837, 200299:16093, 2002; PNAS 99:15837, 2002

Important Determinants of Neuronal Injury by Bilirubin*Important Determinants of

Neuronal Injury by Bilirubin*

l Concentration of unconjugated bilirubin (UCB) and free bilirubin (Bf)

l Concentration of serum albumin

Concentration of hydrogen ion (pH) the

l Concentration of unconjugated bilirubin (UCB) and free bilirubin (Bf)

l Concentration of serum albumin

Concentration of hydrogen ion (pH) the


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l Concentration of hydrogen ion (pH) – the more acidotic (lower pH), the more Bf

l Neuronal susceptibility (prematurity)

l Blood-brain barrier (BBB)???l Note: BBB keeps out bilirubin bound to albumin,

but there is NO a BBB to free bilirubin (Bf)

l Concentration of hydrogen ion (pH) – the more acidotic (lower pH), the more Bf

l Neuronal susceptibility (prematurity)

l Blood-brain barrier (BBB)???l Note: BBB keeps out bilirubin bound to albumin,

but there is NO a BBB to free bilirubin (Bf)

*Volpe,JJ, Neurology of the Newborn, 2001*Volpe,JJ, Neurology of the Newborn, 2001

More on bilirubin: BindingMore on bilirubin: BindingBound vs. unbound or “free” bilirubin

l >99.99% of bilirubin is bound to albumin in the blood

l Bilirubin bound to albumin does not move into brain - it does not cause brain damage.

Bound vs. unbound or “free” bilirubin

l >99.99% of bilirubin is bound to albumin in the blood

l Bilirubin bound to albumin does not move into brain - it does not cause brain damage.


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l The unbound or “free” bilirubin can move from blood into brain tissue and cause brain damage.

l The amount of “free” bilirubin determines brain damage.

l We DO NOT measure free billirubin clinically!!!

l We only measure total bilirubin.

l The unbound or “free” bilirubin can move from blood into brain tissue and cause brain damage.

l The amount of “free” bilirubin determines brain damage.

l We DO NOT measure free billirubin clinically!!!

l We only measure total bilirubin.

Unbound “free” Bilirubin (Bf) vs. Total Serum Bilirubin (TSB)

Unbound “free” Bilirubin (Bf) vs. Total Serum Bilirubin (TSB)

Free unbound bilirubin (UB aka Bf) predicts outcome better than total serum bilirubin (TSB)

� Odell etal, 1970. J Pediatr, 76:12.� Johnson and Boggs,1974. In Phototherapy in the

Newborn: An Overview, eds, Odell GB, Schaffer R, Sionpoulous AP

Free unbound bilirubin (UB aka Bf) predicts outcome better than total serum bilirubin (TSB)

� Odell etal, 1970. J Pediatr, 76:12.� Johnson and Boggs,1974. In Phototherapy in the

Newborn: An Overview, eds, Odell GB, Schaffer R, Sionpoulous AP


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Sionpoulous, AP.

UB predicts ABRs better than TSB� Nakamura etal, Pediatrics 75:703, 1985� Funato etal, Pediatrics 93:50, 1994.� Amin etal, Pediatrics 107:664, 2001.� Ahlfors and Shapiro, Biol Neonate, 80:158, 2001.

Sionpoulous, AP.

UB predicts ABRs better than TSB� Nakamura etal, Pediatrics 75:703, 1985� Funato etal, Pediatrics 93:50, 1994.� Amin etal, Pediatrics 107:664, 2001.� Ahlfors and Shapiro, Biol Neonate, 80:158, 2001.

More on bilirubin: why care about total bilirubin?

More on bilirubin: why care about total bilirubin?

� If free bilirubin causes brain damage, why care about “total bilirubin”, bilirubin bound to albumin in blood?

� Total bilirubin correlates with free bilirubin:� Higher total -> more saturated albumin -> more free

� If free bilirubin causes brain damage, why care about “total bilirubin”, bilirubin bound to albumin in blood?

� Total bilirubin correlates with free bilirubin:� Higher total -> more saturated albumin -> more free


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� Higher total > more saturated albumin > more free

� Total bilirubin is all we can measure (actually, total bilirubin = unconjugated+conjugated bilirubin)

� Though total bilirubin is not perfect, the higher the total bilirubin, the more likely to have brain damage.

� The clinical evidence . . . . .

� Higher total > more saturated albumin > more free

� Total bilirubin is all we can measure (actually, total bilirubin = unconjugated+conjugated bilirubin)

� Though total bilirubin is not perfect, the higher the total bilirubin, the more likely to have brain damage.

� The clinical evidence . . . . .

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Relation Between Maximum Serum Bilirubin Concentration and Kernicterus in Newborns

with Hemolytic Disease*

Relation Between Maximum Serum Bilirubin Concentration and Kernicterus in Newborns

with Hemolytic Disease*No definition or description of kernicterus!


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* From Maisels and data of Mollison PL and Cutbush M, Recent Advances in Pediatrics, 110-132, 1954

* From Maisels and data of Mollison PL and Cutbush M, Recent Advances in Pediatrics, 110-132, 1954

Bhutani Hour-Specific NomogramBhutani Hour-Specific Nomogram

This nomogram does not indicate risk of brain damage, but the risk of a high bilirubin (>17 mg/dl) in the future.

•Bhutani, Johnson, Sivieri, Pediatrics 103:6, 1999•Bhutani, Johnson, Sivieri, Pediatrics 103:6, 1999

High Risk Zone

Low Risk Zone

“1-day-old” Normal at 47 h“1-day-old” Normal at 47 his >95th% at 25his >95th% at 25h

2/6/2007front page

2/6/2007front page

Baby Has Jaundice: Is That a Problem?; Mom of Disabled Boy Pushes for Tests;

Debating Risk of Rare SyndromeRachel Zimmerman. Wall Street Journal. (Eastern edition). New York, N.Y.: Feb 6,


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2007. pg. A.1

Bhutani Hour-Specific NomogramBhutani Hour-Specific Nomogram

8%

33% Risk for Kernicterus with Rh Hemolytic Disease

0%

- Bhutani, Johnson, Sivieri, Pediatrics 103:6, 1999- Bhutani, Johnson, Sivieri, Pediatrics 103:6, 1999

Bhutani Hour-Specific Nomogram & Mollison

and Cutbush 1950

Bhutani Hour-Specific Nomogram & Mollison

and Cutbush 195030-40 mg/dL, 8/11 (73%)

25-29 mg/dL, 4/12 (33%)

19-24 mg/dL, 1/13 (8%)

Bilirubin


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Bhutani, Johnson, Sivieri, Pediatrics 103:6, 1999

10-18 mg/dL 0/24 (0%)Mollison and Cutbush, 1954

2006;117;474-485 Pediatrics

The wide spectrum of response to severe hyperbilirubinemia

*

• Newman etal Pediatrics 111:1303, 2003• Ahlfors and Herbsman Pediatrics 111:1110, 2003• Harris etal Pediatrics 107:1075, 2001.

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Kernicterus: Clinical ExpressionKernicterus: Clinical Expression

• Acute Bilirubin Encephalopathy

• Acute Bilirubin Encephalopathy

• Chronic Bilirubin Encephalopath

• Chronic Bilirubin Encephalopath


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Encephalopathy– Classic Kernicterus

Encephalopathy– Classic Kernicterus

– New Subtypes Auditory, Motor, Subtle• AuditoryNeuropathy, Central

Auditory Processing Disorders• Subtle Neurological, Cognitive,

Learning and Movement Disorders?

– New Subtypes Auditory, Motor, Subtle• AuditoryNeuropathy, Central

Auditory Processing Disorders• Subtle Neurological, Cognitive,

Learning and Movement Disorders?

Clinical: Acute Bilirubin Encephalopathy

Clinical: Acute Bilirubin Encephalopathy

� Lethargy, decreased feeding

� Variable abnormal tone -hyptonia and hypertonia

� High-pitched cry

� Lethargy, decreased feeding

� Variable abnormal tone -hyptonia and hypertonia

� High-pitched cry


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� Retrocollis, opisthotonus, setting sun sign

� Fever

� Seizures (terminal)

� Laboratory� ABR: abnormal I-III & I-V IWI -> decr. Ampl. -> absent� MRI: Bilateral lesions globus pallidus

� Retrocollis, opisthotonus, setting sun sign

� Fever

� Seizures (terminal)

� Laboratory� ABR: abnormal I-III & I-V IWI -> decr. Ampl. -> absent� MRI: Bilateral lesions globus pallidus

Neonatal Jaundice, Brain Damage and the Clinical Spectrum of KernicterusNeonatal Jaundice, Brain Damage and the Clinical Spectrum of KernicterusNeonatal Jaundice, Brain Damage and the Clinical Spectrum of KernicterusNeonatal Jaundice, Brain Damage and the Clinical Spectrum of Kernicterus

Setting Sun Sign in 3 mo old (corrected 2 1/2 mo)

Setting Sun Sign in 3 mo old (corrected 2 1/2 mo)

� b 2008, 34wk GA, antibody to “c”� 3mo 16ds� b 2008, 34wk GA, antibody to “c”� 3mo 16ds


Kansas City Shapiro, VCUMC Pediatric Grand Rounds, September 24, 2008Shapiro, VCUMC Pediatric Grand Rounds, September 24, 2008

Acute Bilirubin Encephalopathy:Take Home Points

Acute Bilirubin Encephalopathy:Take Home Points

• Progression from lethargy to abnormal tone to opisthotonus.

• Acute management:– Triple phototherapy, with two banks of lights as close as


• Acute management:– Triple phototherapy, with two banks of lights as close as


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p p py, gpossible to infant, and a BiliBed (or blanket) underneath.

– Gavage feed with elemental formula to remove bilirubin via stool (Gourley etal, Arch Pediatr Adolesc Med 153:1002,1999)

– Treatment with exchange transfusion may reverse damage!

– It is never too late to treat a neonate with signs of acute bilirubin encephalopathy!

p p py, gpossible to infant, and a BiliBed (or blanket) underneath.

– Gavage feed with elemental formula to remove bilirubin via stool (Gourley etal, Arch Pediatr Adolesc Med 153:1002,1999)

– Treatment with exchange transfusion may reverse damage!


Chronic Kernicterus: ClassicChronic Kernicterus: Classic

1. Movement disorders - athetosis, dystonia, spasticity, “athetoid CP”- basal ganglia (GP, STN), cerebellum,

brainstem nuclei2 A dit S t d f h i l

1. Movement disorders - athetosis, dystonia, spasticity, “athetoid CP”- basal ganglia (GP, STN), cerebellum,

brainstem nuclei2 A dit S t d f h i l


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2. Auditory System - deafness, hearing loss, auditory neuropathy- auditory brainstem nuclei (?nerve)

3. Oculomotor impairments, esp. upgaze- brainstem oculomotor nuclei

4. Dental enamel hypoplasia of deciduous (baby) teeth

2. Auditory System - deafness, hearing loss, auditory neuropathy- auditory brainstem nuclei (?nerve)

3. Oculomotor impairments, esp. upgaze- brainstem oculomotor nuclei

4. Dental enamel hypoplasia of deciduous (baby) teeth

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Kernicterus: SelectivityKernicterus: SelectivitySelective yellow staining of:

� Basal ganglia, esp. globus pallidus� Auditory brainstem nuclei, esp. CN, IC,

SOC� Oculomotor nuclei, esp. nuclei

controlling upgaze� Vestibular nuclei� Cerebellum, esp. purkinje cells� Hippocampus - CA-2 sector, not CA-1 or

Selective yellow staining of:� Basal ganglia, esp. globus pallidus� Auditory brainstem nuclei, esp. CN, IC,

SOC� Oculomotor nuclei, esp. nuclei

controlling upgaze� Vestibular nuclei� Cerebellum, esp. purkinje cells� Hippocampus - CA-2 sector, not CA-1 or

Selective bilirubin staining in the hippocampusSelective bilirubin staining in the hippocampus

CA-2CA-2

- Barmada and Moossy , 1984- Barmada and Moossy , 1984

Selective bilirubin staining in brainstemSelective bilirubin staining in brainstem

� Hippocampus CA 2 sector, not CA 1 or CA-3 (?)

� Hippocampus CA 2 sector, not CA 1 or CA-3 (?)

Classic Kernicterus (cont.)Classic Kernicterus (cont.)

� Cortex = normal => normal intelligence, normal or superior mental function

� May be abnormal sensory integration and sensory motor impairments from involvement of the globus

llid th dit t d th b ll

� Cortex = normal => normal intelligence, normal or superior mental function

� May be abnormal sensory integration and sensory motor impairments from involvement of the globus

llid th dit t d th b ll


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pallidus, the auditory system and the cerebellum

� NOT Mentally Retarded!

Some are highly intelligent but trapped in immobile, dysfunctional bodies, deaf, can’t move, can’t sign, can’t type, can’t communicate . . . Locked in!

pallidus, the auditory system and the cerebellum

� NOT Mentally Retarded!

Some are highly intelligent but trapped in immobile, dysfunctional bodies, deaf, can’t move, can’t sign, can’t type, can’t communicate . . . Locked in!

Classic Kernicterus: Classic Kernicterus: Movement Movement disorder disorder Classic Kernicterus: Classic Kernicterus: Movement Movement disorder disorder

Larocche, 1966

Larocche, 1966

�� AthetosisAthetosis, , ““Athetoid Athetoid CPCP””

�� Dystonia Dystonia �� Hypotonia Hypotonia andand

hypertoniahypertonia�� Not spastic (unless Not spastic (unless

concurrent injury)concurrent injury)

�� AthetosisAthetosis, , ““Athetoid Athetoid CPCP””

�� Dystonia Dystonia �� Hypotonia Hypotonia andand

hypertoniahypertonia�� Not spastic (unless Not spastic (unless

concurrent injury)concurrent injury)

1min 18 sec


Kansas City 33yo, Moderate Kernicterus from Rh disease33yo, Moderate Kernicterus from Rh disease

1min 30 sec

20 sec

Dental Dental enamel enamel dysplasiadysplasia of of primary (primary (““babybaby””))teethteeth

Dental Dental enamel enamel dysplasiadysplasia of of primary (primary (““babybaby””))teethteeth

Kernicterus: Kernicterus: Dental Enamel DysplasiaDental Enamel DysplasiaKernicterus: Kernicterus: Dental Enamel DysplasiaDental Enamel Dysplasia


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18 mo oldMRI at 5mo; T2

Where Kernicterus Damages Control of Movement and Tone

Where Kernicterus Damages Control of Movement and Tone

Can see on MRI: � damages globus pallidus

(GP) part of basal ganglia)

� different from HIE (thalamus and putamen, cerebral cortex

� leads to excessive mo ements incl ding

Can see on MRI: � damages globus pallidus

(GP) part of basal ganglia)

� different from HIE (thalamus and putamen, cerebral cortex

� leads to excessive mo ements incl ding

T1 early T2 late


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STNSTNGPGP

movements, including athetosis and dystoniamovements, including athetosis and dystonia

Cannot see on MRI: � Damages to cerebellar

Purkinje cell layer� Damages to brainstem

nuclei for posture, auditory, vestibular and oculomotor function

Cannot see on MRI: � Damages to cerebellar

Purkinje cell layer� Damages to brainstem

nuclei for posture, auditory, vestibular and oculomotor function

Kernicterus: AuditoryKernicterus: Auditory

Selective bilirubin staining in the brainstem

Selective bilirubin staining in the brainstem

BAEP Changes1. Mild, Reversible

BAEP Changes1. Mild, Reversible


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2. BAEPs may be absent.

Absent BAEPs and normal OAEs = Auditory Neuropathy

2. BAEPs may be absent.

Absent BAEPs and normal OAEs = Auditory Neuropathy

Nwaesei, etal, Nwaesei, etal, PediatricsPediatrics 800, 1984.800, 1984.Nwaesei, etal, Nwaesei, etal, PediatricsPediatrics 800, 1984.800, 1984.

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Auditory Neuropathy -1996

Auditory Neuropathy -1996


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Now known as Auditory Neuropathy Spectrum Disorder (ANSD)

Auditory Neuropathy Spectrum Disorder(Auditory Dys-synchrony)

Auditory Neuropathy Spectrum Disorder(Auditory Dys-synchrony)

Functional Definition:Abnormal ABRs, Normal OAEs

� Normal Cochlea (Inner Ear):

N l OAE ( h i l i t it f i )

Functional Definition:Abnormal ABRs, Normal OAEs

� Normal Cochlea (Inner Ear):

N l OAE ( h i l i t it f i )


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� Normal OAEs (mechanical integrity of inner ear)

� Normal CMs (outer hair cells of inner ear)

� Abnormal Auditory Pathway Function:

� Absent or Abnormal ABRs

� Described in Infants, ~1/2 reported cases have had very significant neonatal hyperbilirubinemia

� Normal OAEs (mechanical integrity of inner ear)

� Normal CMs (outer hair cells of inner ear)

� Abnormal Auditory Pathway Function:

� Absent or Abnormal ABRs

� Described in Infants, ~1/2 reported cases have had very significant neonatal hyperbilirubinemia

Peripheral vs. Central Auditory Systems

Peripheral vs. Central Auditory Systems

Peripheral Auditory SystemOuter Ear, Middle Ear, Inner Ear (hair cells)

Central Auditory

Peripheral Auditory SystemOuter Ear, Middle Ear, Inner Ear (hair cells)

Central Auditory

OuterOuterEarEar

MiddleMiddleEarEar

AuditoryAuditoryNerveNerve

InnerInnerEarEar


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Ce t a ud to ySystemAuditory Nerve, Brainstem, Thalamus (MG), Auditory Cortex (TL)

Ce t a ud to ySystemAuditory Nerve, Brainstem, Thalamus (MG), Auditory Cortex (TL)

Summary: Where Bilirubin Damages the Auditory System

Summary: Where Bilirubin Damages the Auditory System

� Thalamus, cerebral cortex - No!� Brainstem nuclei - YES!

� Cochlear nuclei� Superior olivary complex

Lateral lemnisci

� Thalamus, cerebral cortex - No!� Brainstem nuclei - YES!

� Cochlear nuclei� Superior olivary complex

Lateral lemnisci


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� Lateral lemnisci� Trapezoid bodies� Inferior colliculi

� Auditory nerve and spiral ganglia - ?yes, ?at high levels of toxicity

� Inner ear hair cells - No!

� Lateral lemnisci� Trapezoid bodies� Inferior colliculi

� Auditory nerve and spiral ganglia - ?yes, ?at high levels of toxicity

� Inner ear hair cells - No!II

IIIIII

VV

OAEsOAEsCMCM

BDWBDW

Where Bilirubin Damages the Auditory System in Humans

Where Bilirubin Damages the Auditory System in Humans

Abnormal Abnormal


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ABRsABRs

Normal CM, (OAEs)Normal CM, (OAEs)

Where does Bilirubin Damage theAuditory System? Nerve? Brainstem-Yes!


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ABR

Binaural Interaction ABR

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8

•.

Rance, G., et al., Clinical findings for a group of infants and young children with auditory neuropathy.

-Ear Hear 20:238, 1999.

20 infants� 12 of 5199 from an

early hearing loss

Rance, G., et al., Clinical findings for a group of infants and young children with auditory neuropathy.

-Ear Hear 20:238, 1999.

20 infants� 12 of 5199 from an

early hearing loss

59 mg/dl46 mg/dl27 mg/dl 25 mg/dl22 mg/dl

21 mg/dl *


Kansas City

early hearing loss identification program with high rish neonatal or family histories.

Est. 1/433 newborns at risk for hearing loss have AN

� 8 referred

~1/2 (10/20, 10/16 with etiology) had jaundice as risk factor

early hearing loss identification program with high rish neonatal or family histories.

Est. 1/433 newborns at risk for hearing loss have AN

� 8 referred

~1/2 (10/20, 10/16 with etiology) had jaundice as risk factor

32 mg/dl28 mg/dl *25 mg/dl23 mg/dl *

Berlin et.al. 2003, 260 ptswith ANSD

Berlin et.al. 2003, 260 ptswith ANSD

• 49% due to hyperbilirubinemia– 20% had exchange transfusions– 48% premature– Other: otoxic drugs 29%, ventilator 20%, FH+

• 49% due to hyperbilirubinemia– 20% had exchange transfusions– 48% premature– Other: otoxic drugs 29%, ventilator 20%, FH+


Kansas City

g , ,8%; genetic 16%, 6 with mitochondrial disorders

– 13 with CP; 3 with kernicterus• Improvement in speech & language with:

– No treatment: 5%– Hearing Aids: 15% – Cochlear Implants: 85% improvement

g , ,8%; genetic 16%, 6 with mitochondrial disorders

– 13 with CP; 3 with kernicterus• Improvement in speech & language with:

– No treatment: 5%– Hearing Aids: 15% – Cochlear Implants: 85% improvement

. J Audiol 49, 30-43, 2010

ANAD risk incr 10x with BW <1,000g, 5/100 ANAD, 5/100 SNHL

ANAD risk incr 10x with BW <1,000g, 5/100 ANAD, 5/100 SNHL


Kansas City


Kansas City

J Perinatology 25:54, 2005

Kernicterus - SeverityKernicterus - SeverityAcute

Subacute

ChronicSeve

rity


Kansas City

Shapiro, Seminars in Fetal and Neonatal Medicine 15:157, 2010

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Severe KernicterusSevere Kernicterus

Auditory Predominant KernicterusAuditory Predominant KernicterusAuditory Predominant KernicterusAuditory Predominant Kernicterus

�� B. B. 20012001, 34wk GA, BW , 34wk GA, BW 3174g, 3174g, ApgApg 8/9, A+, 8/9, A+,

Coombs Coombs --�� Absent/Abnormal ABR, Absent/Abnormal ABR,

Acts DeafActs Deaf

�� B. B. 20012001, 34wk GA, BW , 34wk GA, BW 3174g, 3174g, ApgApg 8/9, A+, 8/9, A+,

Coombs Coombs --�� Absent/Abnormal ABR, Absent/Abnormal ABR,

Acts DeafActs Deaf


Kansas City

HypotoniaHypotonia�� Rx: Cochlear ImplantRx: Cochlear Implant

HypotoniaHypotonia�� Rx: Cochlear ImplantRx: Cochlear Implant

15 months15 months15 months15 months

phototherapy

� 1yo male, 34 wk GA, Apg 8/9, AO blood incompat, peak TSB 24.0@4days, photoRx, no X∆

� Failed ABR screen & subsequent ABRs

� 1yo male, 34 wk GA, Apg 8/9, AO blood incompat, peak TSB 24.0@4days, photoRx, no X∆

� Failed ABR screen & subsequent ABRs

Auditory neuropathy + mild motor delay


Kansas City

� Diagnosis: Auditory Neuropathy

� Exam: minimal hypotonia andgross motor delay, hearing impaired, strabismus, upgazeparalysis, dental enamel dysplasia

� Rx: Cochlear implant!

� Diagnosis: Auditory Neuropathy

� Exam: minimal hypotonia andgross motor delay, hearing impaired, strabismus, upgazeparalysis, dental enamel dysplasia

� Rx: Cochlear implant!

Auditory Predominant Auditory Predominant Kernicterus (Kernicterus (Auditory Neuropathy) & occasional muscle cramps

Auditory Predominant Auditory Predominant Kernicterus (Kernicterus (Auditory Neuropathy) & occasional muscle cramps

� b. 1998, 38 wk GA, 2720 g, Apg 7/9

� A-/O+, Rh disease Coombs +

� X∆ transfusion

� b. 1998, 38 wk GA, 2720 g, Apg 7/9

� A-/O+, Rh disease Coombs +

� X∆ transfusion


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� Sequelae:� ABR absent -> Abnl� hearing loss and auditory

neuropathy, � dental enamel hypoplasia, � Hyperactive, ?ADHD� muscle cramps

responsive to benzo

� Sequelae:� ABR absent -> Abnl� hearing loss and auditory

neuropathy, � dental enamel hypoplasia, � Hyperactive, ?ADHD� muscle cramps

responsive to benzo

4 years old4 years old

AN/AD SimulationsAN/AD Simulations


Kansas City http://www.ucihs.uci.edu/com/hesp/newversion/procSim/simulations.htm

Simulation 1: From “Original” to “Profound”

Simulation 2: From "Profound" to "Original"

Simulation 1: From “Original” to “Profound”

Simulation 2: From "Profound" to "Original"

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Kansas City

Auditory Neuropathy:Functional ImplicationsAuditory Neuropathy:Functional Implications

• Neural synchrony may be abnormal:– Problems with sound localization, discriminating

speech in noise or without visual cues (e.g., telephone), auditory memory, ?reading.

– Audiogram may be normal if only neural

• Neural synchrony may be abnormal:– Problems with sound localization, discriminating

speech in noise or without visual cues (e.g., telephone), auditory memory, ?reading.

– Audiogram may be normal if only neural


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Audiogram may be normal if only neural synchrony is involved, thus hearing aids may be harmful!

– ABRA may improve with time (~20-25% AN 2°HB)

•• Speculation: Initial ANAD with Speculation: Initial ANAD with resolutionresolution of abnormal of abnormal ABR may precede or underlie central auditory ABR may precede or underlie central auditory processing disorders (CAPD).processing disorders (CAPD).

Audiogram may be normal if only neural synchrony is involved, thus hearing aids may be harmful!

– ABRA may improve with time (~20-25% AN 2°HB)

•• Speculation: Initial ANAD with Speculation: Initial ANAD with resolutionresolution of abnormal of abnormal ABR may precede or underlie central auditory ABR may precede or underlie central auditory processing disorders (CAPD).processing disorders (CAPD).

HypothesisHypothesis• Neurons are more sensitive to bilirubin

neurotoxicity when they are differentiating vs. before or after (animal studies in cerebellem, auditory system)

• The auditory nervous system develops earlier than the motor system

• Neurons are more sensitive to bilirubin neurotoxicity when they are differentiating vs. before or after (animal studies in cerebellem, auditory system)

• The auditory nervous system develops earlier than the motor system


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earlier than the motor system.• We hypothesized that premature infants

exposed to bilirubin are more likely to have auditory involvement.

• Therefore, we expect a significant relationship of corrected gestational age (GAc) at the time of peak bilirubin to the risk of auditory kernicterus.

earlier than the motor system.• We hypothesized that premature infants

exposed to bilirubin are more likely to have auditory involvement.

• Therefore, we expect a significant relationship of corrected gestational age (GAc) at the time of peak bilirubin to the risk of auditory kernicterus.

46

29 2931

35

41

44

4039

46

30

40

50B

iliru

bin

(m

g/

Bili

rub

in (

mg

/dL

)d

L)

Bili

rub

in (

mg

/B

iliru

bin

(m

g/d

L)

dL

)

ClassicClassic KernicterusKernicterus (KI)(KI)Auditory Predominant KIAuditory Predominant KI

Motor Predominant KIMotor Predominant KI

ClassicClassic KernicterusKernicterus (KI)(KI)Auditory Predominant KIAuditory Predominant KI

Motor Predominant KIMotor Predominant KI

Type of Kernicterus Related Type of Kernicterus Related to Gestational Age to Gestational Age and Peak Total Serum and Peak Total Serum Bilirubin (Bilirubin (n=16n=16))

Type of Kernicterus Related Type of Kernicterus Related to Gestational Age to Gestational Age and Peak Total Serum and Peak Total Serum Bilirubin (Bilirubin (n=16n=16))

26

29 9

2224

25

21

28

10

20

32 34 36 38 40 42

Gestational Gestational Age + Chronological Age Age + Chronological Age (weeks)(weeks)Gestational Gestational Age + Chronological Age Age + Chronological Age (weeks)(weeks)

Tota

l Ser

um

BTo

tal S

eru

m B

Tota

l Ser

um

BTo

tal S

eru

m B

Steven M. Shapiro, M.D.1 and Karen M. Powers, M.D.1,21Dept of Neurology, Virginia Commonwealth University, Richmond, VA and

2Albany Medical Center, Albany, NY

Kernicterus Subtypes and their Association with Signs of Neonatal Encephalopathy*

• 39 cases, 36 (92%) examined by a child neurologist (SMS)• All had extensive medical records review and classified into 1 of

4 subtypes:•• AUDITORYAUDITORY: Auditory-predominant kernicterus with minimal

motor symptoms (n=10),


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y p ( ),•• MOTORMOTOR: Motor-predominant kernicterus with minimal auditory

symptoms (n=4),•• CLASSICCLASSIC: Classical kernicterus with both motor and auditory

symptoms (n=21), •• BINDBIND: Subtle bilirubin-induced neurological disorders (BIND),

children without classic signs of kernicterus but with otherwise convincing evidence of bilirubin encephalopathy (n=4).

• Hypothesis: auditory predominant kernicterus (ANSD) more likely in premature neonates with lower peak TSBs.

*Abstract, Child Neurology Society, Ann Neurol 68 (Suppl.14):S117, 2010

Relationship of Corrected Gestational Age (GAc) and peak Total Serum Bilirubin (TSB) to Outcome (n=36)

Relationship of Corrected Gestational Age (GAc) and peak Total Serum Bilirubin (TSB) to Outcome (n=36)

30

40

50

B (

mg

/dL

)B

(m

g/d

L)


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0

10

20

33 34 35 36 37 38 39 40 41 42

Auditory Motor Classic BIND

Pea

k T

SB

Pea

k T

SB

Corrected GA (weeks)Corrected GA (weeks)

Preterm Term

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11

38

40

week

s)we

eks)

** ***

* = p < 0.05 vs. Auditory** = p < 0.01 vs. Auditory

Corrected Gestational Age (GAc)Mean ± SEM

Corrected Gestational Age (GAc)Mean ± SEM


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34

36

Auditory Classical Motor BIND

Kernicterus GroupKernicterus Group

GAGAcc(w(w


Kansas City


Kansas City

Steven M. Shapiro, M.D.1 and Karen M. Powers, M.D.1,21Dept of Neurology, Virginia Commonwealth University, Richmond, VA and 2Albany Medical Center, Albany, NY

Kernicterus Subtypes and their Association with Signs of Neonatal Encephalopathy

Infants with hyperbilirubinemia who develop with Auditory Predominant Kernicterus are more likely to have had no symptoms in the newborn period (50% auditory vs. 19% with classic kernicterus who have no symptoms, Chi square p < 0.005)

60%

% with NO neonatal symptoms


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0%

20%

40%

60%

Auditory Classical

**Chi square p < 0.005

5 of 5 4 of 21

50%

19%

Conclusions: Subtype differences in GA of exposure to bilirubin

Conclusions: Subtype differences in GA of exposure to bilirubin

Results support our hypotheses that:• The pattern of bilirubin-induced neurological damage

is neurodevelopmentally dependent. • Earlier GA at time of peak TSB suggests premature

neonates are more likely to develop auditory-predominant kernicterus, i.e., ANSD.

Results support our hypotheses that:• The pattern of bilirubin-induced neurological damage

is neurodevelopmentally dependent. • Earlier GA at time of peak TSB suggests premature

neonates are more likely to develop auditory-predominant kernicterus, i.e., ANSD.


Kansas City

p , ,• Higher TSB in classic kernicterus vs. auditory-

predominant and BIND suggests that higher peak TSB causes more severe or widespread sequelae(Interesting that TSB predictive, but biased sample, all subjects had kernicterus).

• Half of infants who develop auditory (ANSD) kernicterus are likely to have had no neurological symptoms in the newborn period.

p , ,• Higher TSB in classic kernicterus vs. auditory-

predominant and BIND suggests that higher peak TSB causes more severe or widespread sequelae(Interesting that TSB predictive, but biased sample, all subjects had kernicterus).

• Half of infants who develop auditory (ANSD) kernicterus are likely to have had no neurological symptoms in the newborn period.

Is neonatal hyperbilirubinemia the cause of a neurodevelopmental disorder (NDD)?

Is neonatal hyperbilirubinemia the cause of a neurodevelopmental disorder (NDD)?History

� Excessively high bilirubin� Minimum: bilirubin > phototherapy level (15-20 mg/dl)* � Stronger evidence: bilirubin > exchange level (20-25 mg/dl)*� Consider other risk factors, (duration, prematurity, sick, pH, Rh)

� Neurological symptoms at time bilirubin high (tone, cry, posturing, eye movements)

E

History� Excessively high bilirubin

� Minimum: bilirubin > phototherapy level (15-20 mg/dl)* � Stronger evidence: bilirubin > exchange level (20-25 mg/dl)*� Consider other risk factors, (duration, prematurity, sick, pH, Rh)

� Neurological symptoms at time bilirubin high (tone, cry, posturing, eye movements)

E


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Exam� Abnormal tone, movements (dysonia, athetosis, incoord)� Hearing impairment, understanding speech in noise, on the

telephone, sound localization, � Abnl eye movemnts, esp. lack of upward gaze (may resolve)� Dental enamel dysplasia (staining/flaking of baby teeth)

Laboratory - specific ABR (BAEP) and MRI findings:� ABR (BAEP) absent or abnormal c/w AN/AD� MRI abnormal globus pallidus ± subthalamic nucleus (T1

hyperintensity early, T2 hyperintensity later)Absent other etiologies (but may be concurrent)

*per AAP Guidelines 2004

Exam� Abnormal tone, movements (dysonia, athetosis, incoord)� Hearing impairment, understanding speech in noise, on the

telephone, sound localization, � Abnl eye movemnts, esp. lack of upward gaze (may resolve)� Dental enamel dysplasia (staining/flaking of baby teeth)

Laboratory - specific ABR (BAEP) and MRI findings:� ABR (BAEP) absent or abnormal c/w AN/AD� MRI abnormal globus pallidus ± subthalamic nucleus (T1

hyperintensity early, T2 hyperintensity later)Absent other etiologies (but may be concurrent)

*per AAP Guidelines 2004

Shapiro, Seminars in Fetal and Neonatal Medicine 15:157, 2010

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12

Mistakes in the treatment of neonatal hyperbilirubinemia - pearls from reviewing medicolegal

cases as an expert witness

Mistakes in the treatment of neonatal hyperbilirubinemia - pearls from reviewing medicolegal

cases as an expert witness• Not believing the bilirubin level from the lab, and delaying treatment

while it is repeated.• Don't delay treatment while waiting for repeat.• Treat with intensive phototherapy, gavage feeding ± hydration, and order a type

and cross match and blood. • If bilirubin drops rapidly to a safe level and the child is asymptomatic, the

exchange transfusion can be cancelled.• Delaying treatment or interrupting phototherapy for diagnostic testing

to determine the risk of an exchange

• Not believing the bilirubin level from the lab, and delaying treatment while it is repeated.

• Don't delay treatment while waiting for repeat.• Treat with intensive phototherapy, gavage feeding ± hydration, and order a type

and cross match and blood. • If bilirubin drops rapidly to a safe level and the child is asymptomatic, the

exchange transfusion can be cancelled.• Delaying treatment or interrupting phototherapy for diagnostic testing

to determine the risk of an exchange


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to determine the risk of an exchange.• Do sepsis workup, LP, ECHO under the lights. • If the baby needs to go off the unit, the lights go with him or her.

• Not examining the baby for signs of acute kernicterus• Using the indirect (or unconjugated) bilirubin instead of the total

serum bilirubin to make treatment decisions.• Allowing the bilirubin to reach potentially dangerous levels.

• It's much easier to prevent bilirubin from rising too high than to treat it when it does.

• Measuring the bilirubin and NOT comparing it to hour-specific norms• Not having a protocol for neonatal hyperbilirubinemia!

• In your practice; in your hospital.

to determine the risk of an exchange.• Do sepsis workup, LP, ECHO under the lights. • If the baby needs to go off the unit, the lights go with him or her.

• Not examining the baby for signs of acute kernicterus• Using the indirect (or unconjugated) bilirubin instead of the total

serum bilirubin to make treatment decisions.• Allowing the bilirubin to reach potentially dangerous levels.

• It's much easier to prevent bilirubin from rising too high than to treat it when it does.

• Measuring the bilirubin and NOT comparing it to hour-specific norms• Not having a protocol for neonatal hyperbilirubinemia!

• In your practice; in your hospital.

Mistakes in the treatment of neonatal hyperbilirubinemia (continued)


• Not putting the Bili lights close enough to the baby• The power is proportional to the distance

• The closer the better, the more skin exposed the better, a Bili Bed underneath is much more powerful than a Bili Blanket

N t li t i t th f il d t bt i i TSB ( T B)

• Not putting the Bili lights close enough to the baby• The power is proportional to the distance

• The closer the better, the more skin exposed the better, a Bili Bed underneath is much more powerful than a Bili Blanket

N t li t i t th f il d t bt i i TSB ( T B)


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• Not listening to the family and not obtaining a TSB (or TcB)

• Tellling family to put baby in the sunlight

• False reassurance over the telephone

• Not examining babies in the light, and missing early jaundice before discharge

• Missing a family history of hereditary spherocytosis or elliptocytosis

• Not listening to the family and not obtaining a TSB (or TcB)

• Tellling family to put baby in the sunlight

• False reassurance over the telephone

• Not examining babies in the light, and missing early jaundice before discharge

• Missing a family history of hereditary spherocytosis or elliptocytosis



Secondary Kernicterus a.k.a.“Critical Illness” Kernicterus a.k.a.

Kernicterus Plus SyndromeNeonate under photoRx for hyperbilirubinemia

Secondary Kernicterus a.k.a.“Critical Illness” Kernicterus a.k.a.

Kernicterus Plus SyndromeNeonate under photoRx for hyperbilirubinemia


Kansas City Shapiro, VCUMC Pediatric Grand Rounds, September 24, 2008Shapiro, VCUMC Pediatric Grand Rounds, September 24, 2008

Neonate under photoRx for hyperbilirubinemia becomes critically ill with NEC, cyanotic congenital heart disease, or other crtical illness and is rushed to OR to save his/her lifePhotoRx is stopped for several hours in OR and recovery room until someone thinks of restarted it. By then then TSB has skyrocketed, and the child ends up with kernicterus plus the original illness.

Neonate under photoRx for hyperbilirubinemia becomes critically ill with NEC, cyanotic congenital heart disease, or other crtical illness and is rushed to OR to save his/her lifePhotoRx is stopped for several hours in OR and recovery room until someone thinks of restarted it. By then then TSB has skyrocketed, and the child ends up with kernicterus plus the original illness.

Take home points (I)Take home points (I)

• A system-wide approach to hyper-bilirubinemia can prevent most cases of severe hyperbilirubinemia

• A system-wide approach to hyper-bilirubinemia can prevent most cases of severe hyperbilirubinemia


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• Acute Bilirubin Encephalopathy is a Neurological Emergency!

• The neonatal neuro exam, ABR (a.k.a. BAEP or BAER), and MRI are useful.

• Acute Bilirubin Encephalopathy is a Neurological Emergency!

• The neonatal neuro exam, ABR (a.k.a. BAEP or BAER), and MRI are useful.

Acute Bilirubin Encephalopathy: Take Home Points (II)

Acute Bilirubin Encephalopathy: Take Home Points (II)


• Acute management:– Triple phototherapy, with two banks of lights as

close as possible to infant, and a BiliBed (much l h h l k ) d h


• Acute management:– Triple phototherapy, with two banks of lights as

close as possible to infant, and a BiliBed (much l h h l k ) d h


Kansas City

p , (more light than blanket) underneath.

– Gavage feed with elemental formula to remove bilirubin via stool (Gourley etal Arch Pediatr Adolesc Med153:184, 1999).

– Treatment with exchange transfusion may reverse some damage!


p , (more light than blanket) underneath.

– Gavage feed with elemental formula to remove bilirubin via stool (Gourley etal Arch Pediatr Adolesc Med153:184, 1999).

– Treatment with exchange transfusion may reverse some damage!


• Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999;103(1):6-14.

• Bhutani VK, Johnson LH, Shapiro SM. Kernicterus in sick and preterm infants (1999-2002): a need for an effective preventive approach. Semin Perinatol. Oct 2004;28(5):319-325.

• Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). Journal of perinatology : official journal of the California Perinatal Association. Feb 2009;29 Suppl 1:S25-45.

• Johnson L, Brown AK, Bhutani VK. BIND-A clinical score for bilirubin induced neurologic dysfunction in newborns. Pediatrics. Sept 1999;104(3 Part 3):746-747.

• Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics Jul 2004;114(1):297-316

References


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Pediatrics. Jul 2004;114(1):297 316.

• Rance G, Beer DE, Cone-Wesson B, et al. Clinical findings for a group of infants and young children with auditory neuropathy. Ear Hear. 1999;20(3):238-252.

• Shapiro SM, Bhutani VK, Johnson L. Hyperbilirubinemia and kernicterus. Clin Perinatol. Jun 2006;33(2):387-410.

• Shapiro SM, Popelka GR. Auditory impairment in infants at risk for bilirubin-induced neurologic dysfunction. Seminars in perinatology. Jun 2011;35(3):162-170.

• Shapiro SM. Chronic bilirubin encephalopathy: diagnosis and outcome. Seminars in fetal & neonatal medicine. Jun 2010;15(3):157-163.

• Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM. Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns. Pediatrics. Feb 2006;117(2):474-485.

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Steven M. Shapiro, MDSteven M. Shapiro, MDsshapirosshapiro@@cmh.educmh.edu

Steven M. Shapiro, MDSteven M. Shapiro, MDsshapirosshapiro@@cmh.educmh.edu

www.kernicterus.orgwww.kernicterus.orgwww.newbornjaundice.orgwww.newbornjaundice.org

www.kernicterus.orgwww.kernicterus.orgwww.newbornjaundice.orgwww.newbornjaundice.org

22. Kernicterus - Shapiro - Children's Mercy Kansas · PDF file10/29/12 2 P.I.C.K. Parents of...

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